The objectives of the proposed research are to exploit the new model system of the renal adenocarcinoma transplanted under the kidney capsule of the estrogen implanted hamster to determine (1) the mechanism of estrogenic tumorigenesis in the kidney, bladder and pituitary, (2) the nature of hormone dependency of the tumor cells and (3) the changes involved as the tumor is transformed from the hormone-dependent state to the autonomous state. We plan to investigate how estrogenic induction and maintenance of tumors differ from the mechanism by which estrogen stimulates its target organs such as the uterus. A further objective is to reach an understanding of the mechanism by which progesterone and antiestrogens, clomiphene and nafoxidine protect the kidney against tumorigenesis. The pituitary of the estrogen implanted hamster undergoes hyperplasia, increases its content of progesterone receptors some seven-fold and finally becomes tumorous. We plan to determine what relationship, if any, exists between the hypertrophy of the pituitary and the neoplastic transformation of the kidney in the estrogen implanted hamster. Using hypophysectomized hamsters bearing DES implants and with renal tumors transplanted under the kidney capsule, we will investigate the possible role of the pituitary and its hormones in inducing and maintaining the renal adenocarcinoma. Does the pituitary secrete some factor required in the carcinogenic process or one that plays a permissive role in tumorigenesis? Experiments paralleling the ones in vivo will be carried out using cell cultures of renal and pituitary tumors and studying the effects of prolactin, ergocornine, gonadotropins and anti-FSH and anti-LH on their growth and regression. We plan to develop an autonomous kidney tumor by serial passages of the estrogen dependent tumor tranplanted under the kidney capsule. We plan to investigate the role of estrogen receptors and progesterone receptors in tumorigenesis and protecting tissues against tumorigenesis using not only the kidney but also the pituitary and bladder of the hamster. These studies should provide improved understanding of the mechanism by which steroids support or inhibit growth of hormone dependent tumors such as tumors of the breast, endometrium and prostate in the human.